Radiation doses and fractionation schedules in non-low-risk ductal carcinoma in situ in the breast (BIG 3-07/TROG 07.01): a randomised, factorial, multicentre, open-label, phase 3 study.

Autor:	Chua BH; Faculty of Medicine and Health, University of New South Wales, Sydney, NSW, Australia; Nelune Comprehensive Cancer Centre, Prince of Wales Hospital, Randwick, NSW, Australia. Electronic address: boon.chua@health.nsw.gov.au., Link EK; Peter MacCallum Cancer Centre, Melbourne, VIC, Australia; Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, VIC, Australia., Kunkler IH; Edinburgh Cancer Research Centre, Institute of Genetic and Molecular Medicine, University of Edinburgh, Western General Hospital, Edinburgh, UK., Whelan TJ; McMaster University, Department of Oncology, Hamilton, ON, Canada; Juravinski Cancer Centre, Hamilton, ON, Canada., Westenberg AH; Radiotherapiegroep Arnhem, Arnhem, Netherlands., Gruber G; Institute for Radiotherapy, Klinik Hirslanden, Zurich, Switzerland., Bryant G; University of Queensland, Brisbane, QLD, Australia., Ahern V; University of Sydney, Sydney, NSW, Australia; Westmead Hospital, Westmead, NSW, Australia., Purohit K; University of Sheffield, Sheffield, UK; Weston Park Hospital, Broomhall, Sheffield, UK., Graham PH; Faculty of Medicine and Health, University of New South Wales, Sydney, NSW, Australia; St George Hospital, Kogarah, NSW, Australia., Akra M; University of Manitoba, Winnipeg, MB, Canada; Cancer Care Manitoba, Winnipeg, MB, Canada., McArdle O; Cancer Trials Ireland, Dublin, Ireland; St Luke's Radiation Oncology Network, Beaumont Hospital, Beaumont, Dublin, Ireland., O'Brien P; University of Newcastle, Newcastle, NSW, Australia; GenesisCare, Gateshead, NSW, Australia., Harvey JA; University of Queensland, Brisbane, QLD, Australia; Princess Alexandra Hospital, Woolloongabba, QLD, Australia., Kirkove C; Université Catholique de Louvain, Brussels, Belgium; Cliniques Universitaires St Luc, Bruxelles, Belgium., Maduro JH; Department of Radiation Oncology, University Medical Centre Groningen, University of Groningen, Groningen, Netherlands., Campbell ID; University of Auckland, Auckland, New Zealand; Waikato Hospital, Hamilton, New Zealand., Delaney GP; Faculty of Medicine and Health, University of New South Wales, Sydney, NSW, Australia; Liverpool Hospital, Liverpool, NSW, Australia., Martin JD; National University of Ireland, Galway, Ireland; University Hospital Galway, Galway, Ireland., Vu TTT; Université de Montréal, Montreal, QC, Canada; Centre hospitalier de l'Université de Montréal, Montreal, QC, Canada., Muanza TM; Department of Oncology, McGill University, Montreal, QC, Canada., Neal A; Royal Surrey County Hospital, Guildford, UK., Olivotto IA; University of Calgary, Calgary, AB, Canada.
Jazyk:	angličtina
Zdroj:	Lancet (London, England) [Lancet] 2022 Aug 06; Vol. 400 (10350), pp. 431-440.
DOI:	10.1016/S0140-6736(22)01246-6
Abstrakt:	Background: Whole breast irradiation (WBI) after conservative surgery for ductal carcinoma in situ (DCIS) reduces local recurrence. We investigated whether a tumour bed boost after WBI improved outcomes, and examined radiation dose fractionation sensitivity for non-low-risk DCIS. Methods: The study was an international, randomised, unmasked, phase 3 trial involving 136 participating centres of six clinical trials organisations in 11 countries (Australia, New Zealand, Singapore, Canada, the Netherlands, Belgium, France, Switzerland, Italy, Ireland, and the UK). Eligible patients were women aged 18 years or older with unilateral, histologically proven, non-low-risk DCIS treated by breast-conserving surgery with at least 1 mm of clear radial resection margins. They were assigned to one of four groups (1:1:1:1) of no tumour bed boost versus boost after conventional versus hypofractionated WBI, or randomly assigned to one of two groups (1:1) of no boost versus boost after each centre prespecified conventional or hypofractionated WBI. The conventional WBI used was 50 Gy in 25 fractions, and hypofractionated WBI was 42·5 Gy in 16 fractions. A boost dose of 16 Gy in eight fractions, if allocated, was delivered after WBI. Patients and clinicians were not masked to treatment allocation. The primary endpoint was time to local recurrence. This trial is registered with ClinicalTrials.gov (NCT00470236). Findings: Between June 25, 2007, and June 30, 2014, 1608 patients were randomly assigned to have no boost (805 patients) or boost (803 patients). Conventional WBI was given to 831 patients, and hypofractionated WBI was given to 777 patients. Median follow-up was 6·6 years. The 5-year free-from-local-recurrence rates were 92·7% (95% CI 90·6-94·4%) in the no-boost group and 97·1% (95·6-98·1%) in the boost group (hazard ratio 0·47; 0·31-0·72; p<0·001). The boost group had higher rates of grade 2 or higher breast pain (10% [8-12%] vs 14% [12-17%], p=0·003) and induration (6% [5-8%] vs 14% [11-16%], p<0·001). Interpretation: In patients with resected non-low-risk DCIS, a tumour bed boost after WBI reduced local recurrence with an increase in grade 2 or greater toxicity. The results provide the first randomised trial data to support the use of boost radiation after postoperative WBI in these patients to improve local control. The international scale of the study supports the generalisability of the results. Funding: National Health and Medical Research Council of Australia, Susan G Komen for the Cure, Breast Cancer Now, OncoSuisse, Dutch Cancer Society, Canadian Cancer Trials Group. Competing Interests: Declaration of interests BHC reports research grants from National Health and Medical Research Council, Susan G Komen for the Cure, Breast Cancer Now, and OncoSuisse Swiss Federation Against Cancer to support the submitted work at Trans-Tasman Oncology Group (Newcastle, NSW, Australia), Centre for Biostatistics and Clinical Trials of Peter MacCallum Cancer Centre (Melbourne, VIC, Australia), and participating cooperative trials groups and sites; and in kind support from Veracyte and NanoString for biomarker testing, outside the submitted work. IHK and AHW report research grants to support the submitted work at the UK Trial Centre, University of Edinburgh (Breast Cancer Now); and research funding from the Dutch Cancer Society to support the submitted work in the Netherlands. TJW reports research funding and non-direct financial support for biomarker testing from Exact Sciences and Genomic Health for ongoing studies. All other authors declare no competing interests. (Copyright © 2022 Elsevier Ltd. All rights reserved.)
Databáze:	MEDLINE
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